Photofrin for Barrett’s Esophagus

Photofrin for Barrett’s Esophagus

ROCKVILLE, MarylandThe Food and Drug Administration has
approved Photofrin (porfimer sodium, Axcan Scandipharm) for the ablation of
high-grade dysplasia in Barrett’s esophagus patients who do not undergo an
esophagectomy. The agency acted less than 2 months after its Gastrointestinal
and Coagulation Drugs Advisory Committee recommended that the FDA approve this
new indication for the photodynamic therapy (PDT) agent.

In Barrett’s esophagus, cells lining the lower portion of
the esophagus are replaced by tissue normally found in the intestine. The
ailment is associated with gastroesophageal reflux. An estimated 25,000 to
35,000 people in North America suffer from high-grade dysplasia associated with
Barrett’s esophagus, and a small number of these patients go on to develop
esophageal adenocarcinoma.

The FDA based its approval of Photo-frin for this condition
on a multicenter clinical trial showing that patients treated with Photofrin-based
PDT in combination with chemotherapy were more likely than patients who
received only a cancer drug to have a complete reversal of their dysplasia.
Moreover, the Photo-frin patients were more likely to be cancer-free 2 years
after treatment than those not treated with PDT.

"The effectiveness of Photofrin PDT in reducing the
long-term risk of esophageal cancer has not been demonstrated," the FDA
said in announcing its marketing approval for the drug.

The FDA first approved Photofrin in 1998 for the partial
reduction of obstruction and palliation in patients with endobronchial
non-small-cell lung cancer (NSCLC). It subsequently approved Photofrin for the
treatment of microin-vasive endobronchial NSCLC in patients for whom surgery
and radiotherapy are not indicated, and for the palliation of patients with
completely obstructing esophageal cancer or those with partial obstruction
whose physicians believe they cannot be treated satisfactorily with an Nd:YAG
laser.

The company’s pivotal study consisted of 208 Barrett’s
esophagus patients treated in North American and Europe in a randomized, controlled,
partially blinded study. In the study, 138 patients received Photofrin PDT plus
omeprazole (Prilosec) and 70 received omeprazole only.

The two-stage treatment begins with an injection of the
drug, an innocuous compound until it is exposed to light. The drug is cleared
from most tissues in 40 to 72 hours, but it is selectively retained in tumors,
skin, and organs of the reticuloendothelial system. Forty to 50 hours after
injection, the dysplasia is exposed to a 680-nm wavelength laser light.

Researchers conducted endoscopic examinations of the
patients every 3 months until they had four negatives tests in a row, and then
semiannually until all patients completed at least 2 years of follow-up. The
length of follow-up ranged from 2.0 to 3.6 years.

The study’s primary endpoint was the complete ablation of
high-grade dysplasia at 24 months: 77% of the Photofrin-treated patients
achieved complete ablation, compared with 39% of the omeprazole-only group (P
< .0001).

An analysis of secondary endpoints showed the following:

Mean ablation duration was 987 days in the Photofrin arm and 98 days in the
omeprazole group.

Twice the proportion of omepra-zole-only patients progressed to esophageal cancer,
compared with those in the Photofrin arm (P = .006).

Patients in both groups who failed to achieve a complete response had approximately a
10-fold higher risk of progressing to cancer than those with a compete
response.

Because skin cells retain Photofrin for up to 90 days,
people treated with the drug must protect their skin and eyes from exposure to
direct sunlight and bright indoor lighting. Photofrin is currently in phase II
studies for the treatment of cholangiocarcinoma.

Your name

E-mail

The content of this field is kept private and will not be shown publicly.